PDGFR?⁺ Cells in Embryonic Stem Cell Cultures Represent the In Vitro Equivalent of the Pre-implantation Primitive Endoderm Precursors.

ABSTRACT: In early mouse pre-implantation development, primitive endoderm (PrE) precursors are platelet-derived growth factor receptor alpha (PDGFR?) positive. Here, we demonstrated that cultured mouse embryonic stem cells (mESCs) express PDGFR? heterogeneously, fluctuating between a PDGFR?+ (PrE-primed) and a platelet endothelial cell adhesion molecule 1 (PECAM1)-positive state (epiblast-primed). The two surface markers can be co-detected on a third subpopulation, expressing epiblast and PrE determinants (double-positive). In vitro, these subpopulations differ in their self-renewal and differentiation capability, transcriptional and epigenetic states. In vivo, double-positive cells contributed to epiblast and PrE, while PrE-primed cells exclusively contributed to PrE derivatives. The transcriptome of PDGFR?⁺ subpopulations differs from previously described subpopulations and shows similarities with early/mid blastocyst cells. The heterogeneity did not depend on PDGFR? but on leukemia inhibitory factor and fibroblast growth factor signaling and DNA methylation. Thus, PDGFR?⁺ cells represent the in vitro counterpart of in vivo PrE precursors, and their selection from cultured mESCs yields pure PrE precursors.

SUBMITTER: Lo Nigro A 

PROVIDER: S-EPMC5311469 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature